Hydroxychloroquine in Decompensated, Treatment-Refractory Noninsulin-Dependent Diabetes Mellitus
Authors: Antonio Quatraro
Journal: Annals of Internal Medicine (1990)

Articles1 May 1990Hydroxychloroquine in Decompensated, Treatment-Refractory Noninsulin-Dependent Diabetes MellitusA New Job for an Old Drug?Antonio Quatraro, MD, Giuseppe Consoli, MD, Mauro Magno, MD, Francesco Caretta, MD, Alberto Nardozza, MD, Antonio Ceriello, MD, Dario Giugliano, MDAntonio Quatraro, MD, Giuseppe Consoli, MD, Mauro Magno, MD, Francesco Caretta, MD, Alberto Nardozza, MD, Antonio Ceriello, MD, Dario Giugliano, MDAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-112-9-678 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptStudy Objective: To evaluate the usefulness and safety of hydroxychloroquine in patients with decompensated, treatment-refractory noninsulin-dependent diabetes mellitus.Design: Prospective, randomized, placebo, double-blind 6-month trial.Patients: Thirty-eight patients with noninsulin-dependent diabetes resistant to commonly used therapies (oral drugs, insulin, combination of insulin and oral drugs).Interventions: Two study groups: one received insulin (n = 22) and the other, glibenclamide (n = 16). In each group, half of the patients were randomly allocated into two subgroups who continued the previous treatment but took either placebo tablets or hydroxychloroquine, 200 mg three times a day. The four subgroups were as follows: insulin and placebo (n = 11); insulin and hydroxychloroquine (n = 11); glibenclamide and placebo (n = 8); and glibenclamide and hydroxychloroquine (n = 8).Measurements and Main Results: At 6 months, relevant and statistically significant improvement occurred in the 11 patients who received the insulin and hydroxychloroquine (glucose profile decrease, -11.7 mmol/L; 95% CI, -13.9 to -9.5, P = 0.001; glycated hemoglobin A1c decrease, -3.3%; 95% CI, -3.9 to -2.7, P = 0.001). No significant changes were seen in patients on placebo. The daily insulin dose in patients treated with the combined insulin and hydroxychloroquine therapy had to be reduced an average of 30%. No important side effects were detected.Conclusions:Combining antidiabetic therapy with hydroxychloroquine in decompensated, treatment-refractory patients with noninsulin-dependent diabetes may help to break the vicious circle of hyperglycemia and lead to better management of the disease....References1. Kahn C. Insulin resistance: a common feature of diabetes mellitus. N Engl J Med. 1986;315:252-4. CrossrefMedlineGoogle Scholar2. DeFronzo R. The triumvirate: beta-cell, muscle and liver. A collusion responsible for NIDDM. Diabetes. 1988;37:667-87. CrossrefMedlineGoogle Scholar3. Quatraro A, Consoli G, Ceriello A, and Giugliano D. Is there a role for chloroquine treatment in diabetes? A three case report [Letter]. Diabete Metab. 1988;14:666-7. MedlineGoogle Scholar4. Smith G, Amos T, Mahler R, and Peters T. Effect of chloroquine on insulin and glucose homeostasis in normal subjects and in patients with non-insulin-dependent diabetes mellitus. Br Med J [Clin Res]. 1987;294:465-7. CrossrefMedlineGoogle Scholar5. Dennis P and Aronson N. The effects of low temperature and chloroquine on 1251-insulin degradation by the perfused rat liver. Arch Biochem Biophys. 1981;212:170-6. CrossrefMedlineGoogle Scholar6. Quatraro A, Consoli G, Minei A, Ceriello A, and Giugliano D. Aggiornamenti in tema di terapia insulinica. Boll Acc Med Pistoiese F Pacini. 1985;54:109-33. Google Scholar7. Quatraro A, Consoli G, Ceriello A, and Giugliano D. Combined insulin and sulfonylurea therapy in non-insulin-dependent diabetics with secondary failure to oral drugs: a one year follow-up. Diabete Metab. 1986;12:315-8. MedlineGoogle Scholar8. Giugliano D, Cozzolino D, and Salvatore T. Altered metabolic and hormonal responses to epinephrine and beta-endorphin in human obesity. J Clin Endocrinol Metab. 1988;67:238-44. CrossrefMedlineGoogle Scholar9. Camerini-Davalos R and Marble A. Incidence and causes of secondary failure in treatment with tolbutamide: experience with 2500 patients treated up to 5 years. JAMA. 1962;181:1-4. CrossrefMedlineGoogle Scholar10. Groop L and Pelkonen R. Treatment failures: a common problem in the management of patients with type-2 diabetes. Acta Endocrinol (Copenh). 1984;105(Suppl 262):131-5. Google Scholar11. Groop L, Pelkonen R, Koskimies S, Bottazzo G, and Doniach D. Secondary failure to treatment with oral antidiabetic agents in non-insulin-dependent diabetes. Diabetes Care. 1986;9:129-33. CrossrefMedlineGoogle Scholar12. Bamber M and Redapth A. Chloroquine and hypoglycaemia [Letter]. Lancet. 1987;1:1211. CrossrefGoogle Scholar13. Polonsky K and Rubenstein A. C-peptide as a measure of secretion and hepatic extraction of insulin. Pitfalls and limitations. Diabetes. 1984;33:486-94. CrossrefMedlineGoogle Scholar14. Giugliano D, Ceriello A, Saccomanno F, Quatraro A, Paolisso G, and D'Onofrio F. Effects of salicylate, tolbutamide, and prostaglandin E2 on insulin responses to glucose in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1985;61:160-6. CrossrefMedlineGoogle Scholar15. Giugliano D, Di Pinto P, and Ceriello A. Glycemic control with an artificial pancreas improves insulin responses to both oral and i.v. glucose in nonobese noninsulin-dependent diabetic subjects. Acta Diabetol Lat. 1985;22:203-13. CrossrefMedlineGoogle Scholar16. Fyles J, Cawthorne M, and Howell S. The effect of chloroquine on receptor internalization in pancreatic islets. Diabetic Med. 1986; 3:P57, 373A. Google Scholar17. Opara E and van Haeften T. Use of chloroquine in adipocyte insulin binding experiments: improved estimation of insulin internalization and receptor bound insulin with linearization of the Scatchard plot [Abstract]. Diabetes. 1987;26(Suppl 1):160A. Google Scholar18. Cynober L, Aussel C, Vaubordolle M, Agneray J, and Ekindjian O. Modulation of insulin action on 2-deoxyglucose uptake by chloroquine in chick embryo fibroblasts. Diabetes. 1987;36:27-32. CrossrefMedlineGoogle Scholar19. Arner P, Einarsson K, Ewerth S, and Livingston J. Studies on the human liver insulin receptor in noninsulin-dependent diabetes mellitus. J Clin Invest. 1986;77:1716-8. CrossrefMedlineGoogle Scholar20. Svenson K, Lundqvist G, Wide L, and Hallgren R. Impaired glucose handling in active rheumatoid arthritis: effects of corticosteroids and antirheumatic treatment. Metabolism. 1987;36:944-8. CrossrefMedlineGoogle Scholar21. Johnson M and Wine A. Hydroxychloroquine therapy in massive total doses without retinal toxicity. Am J Ophthalmol. 1987;104: 139-44. CrossrefMedlineGoogle Scholar22. Unger R and Grundy S. Hyperglycaemia as an inducer as well as a consequence of impaired islet cell function and insulin resistance: implications for the management of diabetes. Diabetologia. 1985; 28:119-21. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Antonio Quatraro, MD; Giuseppe Consoli, MD; Mauro Magno, MD; Francesco Caretta, MD; Alberto Nardozza, MD; Antonio Ceriello, MD; Dario Giugliano, MDFrom Casa di Cura S. Rita, Taranto; and the University of Naples, Naples, Italy. For current author addresses, see end of text. 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